| Eligibility |
Inclusion Criteria:
- Has a histologically or cytologically confirmed advanced or metastatic solid tumor by
pathology report and have received, or been intolerant to, all treatment known to
confer clinical benefit.
- Has measurable disease by Response Evaluation Criteria in Solid Tumors, Version 1.1
(RECIST 1.1) as assessed by local site investigator/radiology. Target lesions situated
in a previously irradiated area are considered measurable if progression has been
demonstrated in such lesions.
- Has a performance status of 0 or 1 on the Eastern Cooperative Oncology Group (ECOG)
Performance Scale.
- Is able to swallow and retain oral medication and has no clinically significant
gastrointestinal abnormalities that might alter absorption.
- Has adequate organ function.
- If male, agree to use a contraception during the treatment period and for at least 120
days after the last dose of study intervention and refrain from donating sperm during
this period.
- If female, is not pregnant or breastfeeding, and is not a woman of childbearing
potential (WOCBP). If a WOCBP, agree to follow the contraceptive guidance during the
treatment period and for at least 120 days after the last dose of study intervention.
- For Human immunodeficiency virus (HIV) infected participants, must have well
controlled HIV on a stable regimen of anti-retroviral therapy (ART). Participants on
ART must have been without changes in drugs or dose modification for at least 4 weeks
prior to study entry.
Exclusion Criteria:
- Has had chemotherapy, definitive radiation, or biological cancer therapy within 4
weeks (2 weeks for palliative radiation) prior to the first dose of study treatment,
or has not recovered to Common Toxicity Criteria for Adverse Events (CTCAE) Grade 1 or
better from any AEs that were due to cancer therapeutics administered more than 4
weeks earlier (this includes participants with previous immunomodulatory therapy with
residual immune-related AEs). Participants receiving ongoing replacement hormone
therapy for endocrine immune-related AEs will not be excluded from participation in
this study.
- Has clinically active central nervous system metastases and/or carcinomatous
meningitis.
- Has had a severe hypersensitivity reaction (= Grade 3) to treatment with a monoclonal
antibody/component of the study treatment, and/or has a history of allergic reactions
attributed to compounds of similar chemical or biologic composition to agents and/or
excipients used in the study.
- Has an active infection requiring therapy.
- Has a history of (non-infectious) pneumonitis that required steroids or has current
pneumonitis.
- Has an active autoimmune disease that has required systemic treatment in the past 2
years except vitiligo or resolved childhood asthma/atopy. Replacement therapy, such as
thyroxine, insulin, or physiologic corticosteroid replacement therapy for adrenal or
pituitary insufficiency, is not considered a form of systemic treatment and is
allowed. Use of non-systemic steroids is permitted.
- Has a diagnosis of immunodeficiency or is receiving systemic steroid therapy or any
other form of immunosuppressive therapy within 7 days prior to allocation.
- Has known Hepatitis B or C infection.
- For HIV infected participants, has a history of Kaposi's sarcoma and/or Multicentric
Castleman's Disease.
- Has undergone major surgery and has not recovered adequately from any toxicity and/or
complications from the intervention prior to starting study therapy.
- Has baseline peripheral neuropathy/paresthesia Grade 1.
- Has any medical, psychiatric, cognitive, or other condition that may compromise the
participant's ability to understand the participant information, give informed
consent, comply with the study protocol, or complete the study, in the opinion of the
treating investigator.
- Participants with clinically significant cardiovascular disease as defined by the
following: 1) Uncontrolled hypertension; 2) Left ventricular ejection fraction (LVEF)
<55%; 3) Symptomatic heart failure (New York Heart Association (NYHA) Grade II to IV),
prior or current cardiomyopathy, or severe valvular heart disease; 4) Uncontrolled
angina; 5) Clinically significant cardiac arrhythmia and/or conduction abnormality =6
months prior to start of study treatment; 6) Myocardial infarction or acute coronary
syndrome =6 months prior to start of study treatment; 7) Mean QT interval calculated
according to the Frederica method (QTcF) interval: Male >450 ms; Female >470 ms.
- Has a history of thromboembolic or cerebrovascular event(s) within 6 months prior to
study enrollment, including transient ischemic attack, cerebrovascular accident, deep
vein thrombosis, or pulmonary embolism.
- Has a neuromuscular disorder associated with an elevated creatine kinase (e.g.,
inflammatory myopathy, muscular dystrophy, amyotrophic lateral sclerosis, spinal
muscular atrophy.
- Has a history of, or current, retinal vein occlusion (RVO) or current risk factors for
RVO (e.g., uncontrolled glaucoma, ocular hypertension, history of hyperviscosity, or
hypercoagulability syndromes).
- Has retinal degenerative disease.
- Has a history or current evidence of any condition, therapy, or laboratory abnormality
that might confound the results of the study, interfere with the participant's
participation for the full duration of the study, make administration of the study
treatments hazardous or make it difficult to monitor adverse effects such that it is
not in the best interest of the participant to participate, in the opinion of the
treating investigator.
- Has a known psychiatric or substance abuse disorder that would interfere with the
Participant's ability to cooperate with the requirements of the study.
- Is pregnant or breastfeeding, or expecting to conceive or father children within the
projected duration of the study.
- Has received a live-virus vaccine within 28 days of planned treatment start. Seasonal
flu vaccines that do not contain live virus are permitted.
- Is currently participating and receiving study treatment in a study of an
investigational agent or has participated and received study treatment in a study of
an investigational agent or has used an investigational device within 28 days of
administration of selumetinib.
- Is a WOCBP who has a positive urine pregnancy test within 24 hours before the first
dose of study treatment.
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